Download Lung Cancer by Ossama Tawfik

Lung Cancer
Ossama Tawfik, MD, PhD
Professor, Vice Chairman
Director of Anatomic &Surgical Pathology
University of Kansas School of Medicine
Alexandria, Egypt July 1- 3, 2008
OBJECTIVES
Describe and list the main different histologic
types of carcinomas of the lung.
Describe and list the main clinical and
histopathologic features of lung cancer.
List factors associated with the different types
of lung cancer.
Describe and list the main clinical and
histopathological features of mesothelioma.
Lung Cancer
•
•
Peak incidence in 6th
and 7th decades
M:F = 2:1
Common Risk Factors for
Lung Cancer
Cigarette smoking
Asbestos exposure
Radiation
Aromatic hydrocarbons
Metals: nickel, arsenic, chromate,
beryllium
Previous history of lung cancer
Pathogenesis
K-ras mutation, cigarette smoking (nonsmall cell Ca)
Myc overexpression (small cell Ca)
p53, Rb mutations (small cell Ca, nonsmall cell Ca)
bcl-2 expression (SCC- adenoCa)
Clinical Features
Local
z Cough, dyspnea, hemoptysis, pain, pneumonia, pleural
effusion
z Pancoast tumor (apex of lung)
z Pancoast syndrome (cervical sympathetic nerves
paralysis
z Horner syndrome
z endophthalmos, ptosis, miosis, anhidrosis
Mediastinal
z Superior vena cava syndrome
Metastasis
z LNs, brain, bone, liver, ADRENALs
Paraneoplastic Syndromes
Gross Classification
Central group: neoplasms arising in
major bronchi, segmental bronchi or
divisions up to 1 mm in diameter
2. Peripheral group: neoplasms arising
in lung parenchyma where
bronchioles are less than 1 mm in
diameter
1.
Histological Classification of
Lung Tumors
I.
Epithelial tumors
A. Benign
1. Papillomas
2. Adenomas
B. Dysplasia, CIS
C. Malignant, Epithelial
1.
2.
3.
4.
5.
6.
7.
Squamous cell carcinoma
Small cell carcinoma
Adenocarcinoma
Large cell carcinoma
Adenosquamous carcinoma
Carcinoid tumor
Others
I.
II.
III.
IV.
Soft Tissue Tumors
Mesothelioma
MetastaticTumors
Miscellaneous Tumors
A. Carcinosarcoma
B. Pulmonary blastoma
C. Others
V.
Other Benign Lesions
A. Hamartoma
Common Lung Cancers
Squamous cell carcinoma (25 to 40%)
Adenocarcinoma (25 to 40%)
Small cell carcinoma (20 to 25%)
Large cell carcinoma (10 to 15%)
Squamous Cell Carcinoma
Clinical Features
Hemoptysis, cough
Symptoms due to obstruction:
recurrent pneumonia, atelectasis
Superior vena cava syndrome
Pancoast syndrome/Pancoast tumor
Horner syndrome
Hypercalcemia (sec of PTH-like sub)
Squamous Cell Carcinoma
Closely linked to smoking
More frequent in males
Usually central in location (75
to 95%)
Squamous Cell Carcinoma
LUL replaced by
tumor
LLL bronchus
Left mainstem
bronchus with tumor
Squamous Cell Carcinoma
with Cystic cavitary changes
Keratin Pearl
Desmoplastic
(fibrous) stroma of
tumor
Keratin Pearls
in Squamous Cell Carcinoma
Intercellular bridges
in Squamous Cell Carcinoma
MIB-1 Immunostain
EGFR Immunostain
Squamous Cell Carcinoma
Prognosis
Clinical stage most important
prognostic factor
Overall 5 year survival is
about 15%
Squamous Cell Carcinoma
Well, Moderately, poorly differentiated Ca
Keratinizing or non keratinizing
90% central - 10% peripheral
Carcinoma in situ
Association w smoking
Paraneoplastic syndrome – hypercalcemia
Rx: Surgical
Adenocarcinoma
Increasing incidence
Usually peripheral (75%)
May be associated with scars?
Most common type in women
Upper Lobe Adenocarcinoma with
Invasion of Chest Wall
Peripheral tumor
invading rib
Cut section of rib &
intercostal muscles
Adenocarcinoma
Histologic Subtypes
Acinar adenocarcinoma
2. Solid carcinoma with mucous
formation (formerly large cell
carcinoma)
3. Papillary adenocarcinoma
4. Bronchiolo-alveolar carcinoma
1.
Adenocarcinoma (Acinar Type)
Desmoplastic stroma
Gland lumens filled with
mucinous secretions (gray)
Acinar
Adenocarcinoma
Adenocarcinoma
Solid Type
Adenocarcinoma (Papillary Type)
Papillary
structures
Bronchioloalveolar
Carcinoma
M:F = 1:1
Mucinous and Non-mucinous
Types
3 growth patterns grossly:
1) Solitary mass (coin lesion)
2) Multiple nodules
3) Multicentric diffuse infiltrate
Multicentric BAC
Bronchioloaveolar Carcinoma
Pre-existent
alveolar walls
Tumor cells lining
up on alveolar walls
Adenocarcinoma
Prognosis
Survival primarily dependent
on clinical stage
Overall 5 year survival 1520%
Bronchioalveolar Carcinoma
Prognosis
5 year survival 42%
Worse prognosis for diffuse
form
Adenocarcinoma
Peripherally located
Well, moderately, poorly differentiated
Primary Vs. metastatic lesions (TTF-1 –90%+)
Variants:
z Bronchogenic adenocarcinoma
z “Scar” carcinoma
z Bronchiolo-alveolar carcinoma
z Others: papillary, solid, mucinous
Neuroendocrine Tumors of
the Lung
Mature carcinoid tumor
Atypical carcinoid tumor
Large-cell neuroendocrine
carcinoma
Small-cell carcinoma
Bronchial Carcinoids
•
•
•
•
Neuroendocrine neoplasm
Account for 1-5% of all lung
tumors
M=F
Wide age range;
average age 45 yrs
Bronchial Carcinoids
Three groups:
• Central carcinoid
• Peripheral carcinoid
• Atypical carcinoid
Central Bronchial Carcinoid
•
•
•
Most frequent type (90% of bronchial
carcinoids)
Arise in subsegmental or larger
bronchi as polypoid exophytic mass
projecting into bronchial lumen.
Usually invade bronchial wall with
variable invasion of adjacent lung
Clinical Features of
Carcinoid Syndrome
•
•
•
•
•
•
•
Attacks of skin flushing
Cyanosis
Diarrhea
Broncho constriction
Sudden hypotension
Edema
Right-sided heart valve abnormalities
Central Carcinoid: Gross
and micro H and E
Carcinoid Tumor
H and E
Chromogranin
Atypical Carcinoid Tumor
Increased mitotic activity (2-10/ 10
HPFs)
Tumor necrosis
Increased cellularity
Nuclear pleomorphism,
hyperchromasia, high n/c ration
Prognosis of Bronchial
Carcinoids
40% metastasize to regional
lymph nodes
5-10% metastasize to liver
5 to 10 yr. survival rates: 50-95%
Small Cell Carcinoma
“Oat cell carcinoma”
Male predominance
(M/F 2:1)
Closely associated
with smoking
Usually central in
location
Small Cell Carcinoma
Opened bronchus
bronchus
Opened
containing tumor
tumor
containing
Tumor
Small Cell Carcinoma
Oat cell type
Intermediate type
Combined
Oat Cell Type
Combined Small Cell & Sq.Ca
Small cell ca
Squamous cell ca
Small Cell Carcinoma
Frequently associated with
paraneoplastic syndrome
Majority of tumors are already
metastatic at time of diagnosis
Treatment of choice:
chemotherapy/radiation
5 year survival: 1-4%
Common Paraneoplastic
Syndromes
1.
2.
3.
4.
5.
6.
Cushing's syndrome (ACTH)
Inappropriate ADH secretion
Carcinoid syndrome
Hypercalcemia (PTH)
Gynecomastia (Gonadotropin)
Acromegaly (GH)
Large Cell Carcinoma
Poorly differentiated carcinoma
without evidence of squamous
or glandular differentiation by
light microscopy
Electron microscopy may show
squamous or glandular features
Clusters of large
malignant cells
Lymphocytes
Metastatic Neoplasms
Lung most frequent site (other
than LN)
Patterns of Metastasis:
1. Multiple nodules
2. Lymphangitic metastasis
3. Solitary
Metastatic Neoplasms
Ovarian adenocarcinoma
Breast cancer
Prostatic cancer
Colonic adenocarcinoma
Renal carcinoma
Melanoma, lymphoma, sarcoma
Metastatic Osteosarcoma
Metastatic
Melanoma
Malignant Mesothelioma
1.
2.
3.
4.
Increasing in frequency
Asbestos exposure (20 – 40 yr lag)
Usually have pleural effusion
Most frequent in 40 – 70 year age
group
5. M:F = 2 to 3:1
Malignant Mesothelioma: Gross
Pleural tumor
encasing lung
LLL
LUL
Tumor extending along interlobar fissure
Diaphragm
with tumor
Malignant Mesothelioma: Biphasic
Epithelial-like cells
Spindle cells
Lung Cancer Survival
TUMOR TYPE
Squamous Cell Ca.
Adenocarcinoma
Small Cell Carcinoma
Large Cell Carcinoma
Overall Survival
5 YR. SURVIVAL
15%
15-20%
1-4%
3%
8-10%
Metastasis and complications
1.
2.
3.
4.
5.
Regional lymph
nodes (most
cases)
Liver 30-50%
Adrenal >50%
Bone 15-20%
Brain 20%
Pneumonia
Lung abscess
Bleeding
Effects of
metastasis on
other organs